Necklace-shaped physiological monitor

ABSTRACT

The invention provides a neck-worn sensor (referred to herein as the ‘necklace’) that is a single, body-worn system that measures the following parameters from an ambulatory patient: heart rate, pulse rate, pulse oximetry, respiratory rate, temperature, thoracic fluid levels, stroke volume, cardiac output, and a parameter sensitive to blood pressure called pulse transit time. From stroke volume, a first algorithm employing a linear model can estimate the patient&#39;s pulse pressure. And from pulse pressure and pulse transit time, a second algorithm, also employing a linear algorithm, can estimate systolic blood pressure and diastolic blood pressure. Thus, the necklace can measure all five vital signs along with hemodynamic parameters. It also includes a motion-detecting accelerometer, from which it can determine motion-related parameters such as posture, degree of motion, activity level, respiratory-induced heaving of the chest, and falls.

CROSS REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/436,703, filed Jun. 10, 2019 which is a continuation of U.S. patentapplication Ser. No. 14/184,608, filed Feb. 19, 2014, now U.S. Pat. No.10,314,496, which claims the benefit of U.S. Provisional Application No.61/767,181, filed Feb. 20, 2013, each of which is hereby incorporated inits entirety including all tables, figures, and claims.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to sensors that measure physiologicalsignals from patients.

Description of the Related Art

Medical devices can measure time-dependent electrocardiograms (ECG) andthoracic bioimpedance (TBI) waveforms from patients. Such devicestypically connect to disposable electrodes that adhere to the patient'sskin and measure bioelectric signals. Analog circuits within the deviceprocess the signals to generate the waveform, which with furtheranalysis yields parameters such as heart rate (HR), thoracic fluidlevels, stroke volume (SV), cardiac output (CO), and respiratory rate(RR). Other systems within the medical devices measure vital signs suchas pulse oximetry (SpO2), pulse rate (PR), and temperature (TEMP).Typically the medical device is remote from the patient, and connects toa body-worn sensor through a cable. Adhesive electrodes are sensors thatmeasure ECG and TBI waveform; these are typically worn on the patient'schest or legs. Patients can wear an optical sensor on their fingers orear to measure photoplethysmogram (PPG) waveforms, which are thenprocessed to yield SpO2 and PR. Temperature is typically measured with athermometer inserted in the patient's mouth.

Devices that measure ECG and TBI waveforms are often used tocharacterize patients suffering from congestive heart failure (CHF). CHFoccurs when the heart is unable to sufficiently pump and distributeblood to meet the body's needs. The condition is typically preceded byan increase of fluid in the thoracic cavity, and can be characterized byshortness of breath, swelling of the legs and other appendages, andintolerance to exercise. It affects nearly 5.3 million Americans and hasan accompanying cost of somewhere between 30-50 billion dollars, withroughly 17 billion dollars attributed to hospital readmissions. Suchevents are particularly expensive to hospitals, as readmissionsoccurring within a 30-day period are not reimbursable by Medicare orprivate insurance as of October 2012.

In medical centers, CHF is typically detected using Doppler/ultrasound,which measures parameters such as SV, CO, and ejection fraction (EF).Gradual weight gain measured with a simple scale is one method toindicate CHF in the home environment. However, this parameter istypically not sensitive enough to detect the early onset of CHF, aparticularly important time when the condition may be ameliorated by achange in medication or diet.

SV is the mathematical difference between left ventricular end-diastolicvolume (EDV) and end-systolic volume (ESV), and represents the volume ofblood ejected by the left ventricle with each heartbeat; a typical valueis about 80 mL. EF relates to EDV and ESV as described below in Eq. 1,with a typical value for healthy individuals being about 50-65%, and anejection fraction of less than 40% indicating systolic heart failure.

$\begin{matrix}{{EF} = {\frac{SV}{EDV} = \frac{{EDV} - {ESV}}{EDV}}} & (1)\end{matrix}$

CO is the average, time-dependent volume of blood ejected from the leftventricle into the aorta and, informally, indicates how efficiently apatient's heart pumps blood through their arterial tree; a typical valueis about 5 L/min. CO is the product of HR and SV, i.e.:

CO=SV×HR   (2)

CHF patients, in particular those suffering from systolic heart failure,may receive implanted devices, such as pacemakers and/or implantablecardioverter-defibrillators, to increase EF and subsequent blood flowthroughout the body. These devices also include technologies called‘OptiVol’ (from Medtronic) or ‘CorVue’ (St. Jude) that use circuitry andalgorithms within the implanted device to measure the electricalimpedance between different leads of the pacemaker. As thoracic fluidincreases in the CHF patient, the impedance typically is reduced. Thusthis parameter, when read by an interrogating device placed outside thepatient's body, can indicate the onset of heart failure.

Corventis Inc. has developed the AVIVO Mobile Patient Management (MPM)System to characterize ambulatory CHF patients. AVIVO is typically usedover a 7-day period, during which it provides continual insight into apatient's physiological status by steadily collecting data andwirelessly transmitting it through a small handheld device to a centralserver for analysis and review. The system consists of three parts: 1)The PiiX sensor, a patient-worn adhesive device that resembles a large(approximately 15″ long) bandage and measures fluid status, ECGwaveforms, HR, RR, patient activity, and posture; 2) The zLink MobileTransmitter, a small, handheld device that receives information from thePiix sensor and then transmits data wirelessly to a remote server viacellular technology; and 3) the Corventis Monitoring Center, where dataare collected and analyzed. Technicians staff the Monitoring Center,review the incoming data, and in response generate clinical reports madeavailable to prescribing physicians by way of a web-based userinterface.

In some cases, physicians can prescribe ambulatory monitors to CHFpatients. These systems measure time-dependent ECG waveforms, from whichHR and information related to arrhythmias and other cardiac propertiesare extracted. They characterize ambulatory patients over short periods(e.g. 24-48 hours) using ‘holter’ monitors, or over longer periods (e.g.1-3 weeks) using cardiac event monitors. Conventional holter or eventmonitors typically include a collection of chest-worn ECG electrodes(typically 3 or 5), an ECG circuit that collects analog signals from theECG electrodes and converts these into multi-lead ECG waveforms; and aprocessing unit that then analyzes the ECG waveforms to determinecardiac information. Typically the patient wears the entire system ontheir body. Some modern ECG-monitoring systems include wirelesscapabilities that transmit ECG waveforms and other numerical datathrough a cellular interface to an Internet-based system, where they arefurther analyzed to generate, for example, reports describing thepatient's cardiac rhythm. In less sophisticated systems, the ECGmonitoring system is worn by the patient, and then returned to a companythat downloads all relevant information into a computer, which thenanalyzes it to generate the report. The report, for example, may beimported into the patient's electronic medical record (EMR). The EMRavails the report to cardiologists or other clinicians, who then use itto help characterize the patient.

SUMMARY OF THE INVENTION

The invention provides a neck-worn sensor (referred to herein as the‘necklace’) that is a single, body-worn system that measures thefollowing parameters from an ambulatory patient: HR, PR, SpO2, RR, TEMP,thoracic fluid levels, SV, CO, and a parameter sensitive to bloodpressure called pulse transit time (PTT). From SV, a first algorithmemploying a linear model can estimate the patient's pulse pressure (PP).And from PP and PTT, a second algorithm, also employing a linearalgorithm, can estimate systolic blood pressure (SBP) and diastolicblood pressure (DBP). Thus, the necklace can measure all five vitalsigns (HR/PR, SpO2, RR, TEMP, and SBP/DPB) along with hemodynamicparameters (SV, CO). It also includes a motion-detecting accelerometer,from which it can determine motion-related parameters such as posture,degree of motion, activity level, respiratory-induced heaving of thechest, and falls. The necklace can operate additional algorithms toprocess the motion-related parameters to measure vital signs andhemodynamic parameters when motion is minimized and below apre-determined threshold, thereby reducing artifacts. Moreover, itestimates motion-related parameters such as posture to improve theaccuracy of calculations for vital signs and hemodynamic parameters.

The necklace measures all of the above-mentioned properties whilefeaturing a comfortable, easy-to-wear form factor that resembles a pieceof conventional jewelry. It is lightweight (about 100 grams) anddesigned to resemble something other than a conventional medical device.During use, it simply drapes around the neck, and then is held in placeby a pair of customized electrodes that measure physiological signals,described in more detail below.

The necklace measures ECG and TBI waveforms using electrical circuitrydisposed in the strands that hold it in place. On a bottom surface ofthe circuit is a customized electrode holder that connects through amagnetic field to a mated set of magnets in a custom electrode. Theelectrodes contain three separate electrode regions to measure ECG andTBI waveforms. The electrode holders magnetically hold the electrodes inplace while providing the necessary electrical couplings. During use,the electrodes are simply held proximal to the electrode holders.Magnetic fields between these components cause the electrodes to easilysnap into place. Additionally, the magnets providing the magneticinterface also include a conductive metal coating, meaning they conductelectrical signals sensed by the electrodes into the TBI and ECG analogcircuits.

Upper electrodes in each electrode holder supply a drive current for theTBI measurement, while lower electrodes measure a voltage representingthe product of the injected drive current and internal impedance in thepatient's thoracic cavity. The signals are processed by the TBI analogcircuit to generate an analog TBI waveform, which is then sent to ananalog-to-digital converter within the left-hand side of the necklacestrand for digitization. The middle electrode in each of the three-partelectrodes measure signals that pass to an ECG circuit in the right-handstrand, where they are processed with a differential amplifier togenerate an analog ECG waveform, which is then sent to theanalog-to-digital converter for digitization. Once digitized, both theTBI and ECG waveforms are processed as described below to determine bothvital signs and hemodynamic parameters.

Strands disposed on both the left and right-hand sides of the patient'sneck feature analog circuitry (right-hand side) and digital circuitry(left-hand side). This circuitry, which is typically disposed onnon-flexible fiberglass circuit boards, is connected with flexiblecircuitry embedded in thin, Kapton films. Typically both the flexibleand non-flexible circuits are embedded in a soft, silicone rubber film.Alternating non-flexible and flexible circuitry provides the necklacewith all the necessary electronics while allowing it to comfortably bendaround the patient's neck.

Other circuitry for temperature, motion, SpO2, wireless datatransmission, and data processing are included in strands of thenecklace, as is described in more detail below.

The necklace's form factor is designed for comfort and ease of use, withthe ultimate goal of improving patient compliance so that theabove-mentioned parameters can be measured in a continuous manner and ona day-to-day basis. The system is targeted for elderly, at-homepatients, e.g. those suffering from chronic conditions such as CHF,diabetes, and chronic obstructive pulmonary disease (COPD). It is wornaround the patient's neck, a location that is unobtrusive, comfortable,removed from the hands, and able to bear the weight of the sensorwithout being noticeable to the patient. The neck and thoracic cavityare also relatively free of motion compared to appendages such as thehands and fingers, and thus a sensor affixed to this location minimizesmotion-related artifacts. Moreover, as described above, such artifactsare compensated for, to some degree, by the accelerometer within thenecklace.

The necklace also features other components that simplify it and improveease of use. For example, it includes a Bluetooth transmitter that sendsdata (e.g. waveforms and numerical values) to the patient's existingcellular telephone; from there, the data can be forwarded to a physicianfor further review. The electrodes and associated electrode holdersinclude mated magnets so that, prior to a measurement, the electrodessimply ‘snap’ into place, thus eliminating the need for cumbersome snapsand rivets that can be difficult for elderly patients to connect. Abattery housed in a bottom portion of the necklace (i.e., where anamulet would connect to a conventional necklace) can be easily replacedwithout removing the necklace's strands, which attach to the patientwith the magnetically connected electrodes. In this manner, a freshbattery can be installed when the original battery begins to run low onpower, thus allowing the necklace to be used continuously for extendedperiods of time (e.g. for patient monitoring in a hospital or nursinghome).

SpO2 is the one vital sign that is not measured directly from the neck.Here, a circuit board for processing PPG waveforms used to calculateSpO2 and PR resides in the necklace. During a measurement, an opticalsensor, which includes separate light-emitting diodes operating in thered (e.g. 600 nm) and infrared (e.g. 800 nm) spectral regions, connectsthrough a flexible cable to the circuit board. The optical sensor simplyclips to the base of the ear, where it measures PPG waveforms with bothred and infrared wavelengths. An algorithm operating on themicroprocessor within the necklace processes these data to determineSpO2, as is described in more detail below. Additionally, PR can becalculated from neighboring pulses in the PPG waveform.

PTT, as described above, correlates inversely with both SBP and DPB. Itis calculated from a time difference between the maximum of the ECGwaveform (called the QRS complex), and a fiducial point on the TBIwaveform (e.g. the onset of the waveform, or the point of maximum slope,as determined from the maximum of the mathematical derivative).Alternatively, PTT can be measured from the ECG QRS and a similarfiducial point on the PPG waveform measured from the ear. Oncedetermined, the inverse of PTT can be used with a calibrationmeasurement (e.g. one performed with a conventional cuff-based bloodpressure monitor) to estimate SBP/DBP. Alternatively, the un-calibratedvalue of PTT can be used to estimate trends in SBP and DPB.

It is well know that PP correlates with SV, and typically thiscorrelation is defined by a single, linear relationship that extendsacross all patients. Additionally, changes in SV correlate extremelywell with changes in PP. Thus, TBI-determined SV yields an independentmeasurement of PP, and this in turn can increase the accuracy of SDP andDBP.

In one aspect, the invention provides a system for measuring PTT that isworn around a patient's neck. The system features an ECG system with ananalog ECG circuit in electrical contact with at least two ECGelectrodes that measure an analog ECG waveform. Also included in thenecklace is an impedance system with an analog impedance circuit inelectrical contact with at least two impedance electrodes that measurean analog impedance waveform. A digital processing system, featuring amicroprocessor and analog-to-digital converter, receive the analog ECGand impedance waveforms, and then digitize them to form correspondingdigital waveforms. A cable, worn around the patient's neck, houses boththe analog ECG and impedance circuits, and the digital processingsystem. An algorithm running on the microprocessor processes the digitalECG waveform to determine a first time point, and the digital impedancewaveform to determine a second time point. It then analyzes the firstand second time points to determine PTT.

In embodiments, the cable that houses the above-mentioned circuitelements typically includes a collection of wires that connect the ECGand impedance systems to the digital processing system. Such a systemminimizes cable clutter around the patient's neck, as the componentsthat make up the necklace are also carefully designed electricalconductors. The wires can be embedded in a flexible circuit orconductor. Within the necklace, these flexible elements typicallyalternate with non-flexible circuit boards that support the ECG,impedance, and digital processing systems.

In embodiments, the cable draped around the patient's neck includes afirst ECG electrode in a first segment that contacts a first side of thepatient's chest, and a second ECG electrode in a second segment thatcontacts a second, opposing side of the patient's chest. The first andsecond segments can also include, respectively, first and secondimpedance electrodes that contact the chest just below the ECGelectrodes.

In typical embodiments, the impedance system includes four distinctelectrodes: a first and current-injecting electrode, and a first andsecond voltage-measuring electrode. Typically both the first and secondsegments include the current-injecting and voltage-measuring electrodes,along with an ECG electrode, as described above.

In embodiments, the necklace includes a battery system that powers theECG, impedance, and digital processing system. Like these systems, thebattery is within the necklace's cable, and is typically located betweenthe first and second segments, where it resembles an amulet. The batterysystem features a connector that is mated to a similar connector in thenecklace so that the battery system can be detached, removed, andreplaced with another battery.

In other embodiments, the necklace includes a wireless transceiverwithin the cable. Typically this system operates on a protocol such asBluetooth or 802.11a/b/g/n. It can also include a USB connector inelectrical contact with a flash memory system.

In another aspect, the invention provides a method for measuring PTT.Such a method is typically accomplished with computer code programmedinto the microprocessor that runs an algorithm. The algorithm determinesa first time point from the digital ECG waveform, and a second timepoint from the digital impedance waveform. It then calculates PTT fromthe difference between the first and second time points.

In embodiments, the algorithm involves taking a mathematical firstderivative of the digital impedance waveform, and then processing themathematical first derivative to determine the second time point. Forexample, the algorithm can detect a maximum value of the mathematicalfirst derivative, which is a point representing the maximum flow rate ofblood through the aorta, and use this for the second time point. Thealgorithm can also use other fiducial points from the mathematicalderivative for the second time point, e.g. an inflection point or zeropoint crossing. For the first time point, the algorithm typically usesthe ECG QRS complex, which can be easily detected from the digital ECGwaveform using a beat-picking algorithm.

Once PTT is determined, the algorithm can use it to estimate a bloodpressure value. Without using a calibration of some sort, PTT can yieldtrends in both SBP and DPB. In other embodiments, the algorithmcollectively processes PTT with a calibration value to determine anabsolute blood pressure value. For example, the necklace can receive thecalibration value with the internal wireless transceiver, and then usethis to calculate the absolute blood pressure value.

In a related aspect, the invention provides a method to determine PTTand then blood pressure using a PPG waveform measured with a pulseoximetry circuit within the necklace. Typically the pulse oximetrycircuit connects through a cable to an optical sensor that connects toone of the patient's ears. Collectively, these components form a pulseoximetry system. The optical sensor features a first light sourceoperating in the red spectral region, and a second light sourceoperating in the infrared spectral region. During a measurement, bothlight sources generate radiation that passes through a portion of thepatient's ear (e.g. the earlobe), where it is detected with alight-sensitive diode (e.g. a photodiode) to generate PPG waveforms. Analgorithm processes digital versions of waveforms generated with red andinfrared radiation to calculate a value of SpO2.

In another aspect, the invention provides a system that measures PTTduring periods of motion. Here, the necklace includes a motion sensor(e.g. an accelerometer) within the cable. It measures a motion signalfrom the patient. Using algorithms similar to those described above, themicroprocessor within the necklace determines a PTT value from the ECGand impedance (or PPG) waveforms when the motion signal, or a processedversion thereof, is below a pre-determined threshold value. This valueindicates a degree of motion that may corrupt waveforms measured by theimpedance or pulse oximetry systems, as these waveforms are particularlysensitive to motion.

In yet another aspect, the necklace measures RR, and it includes amotion sensor that measures a motion signal which the necklace processesin a manner similar to that described above. In this way, RRmeasurements are made without containing motion-related artifacts. Thenecklace measures RR from the impedance waveform, e.g. by taking amathematical first derivative of the waveform and then counting fiducialpoints (e.g. maximum values, inflection points, or zero point crossings)to determine RR. In other embodiments, an algorithm calculates afrequency-domain transform (e.g. a Fourier Transform) of the digitalimpedance waveform, and then processes a peak in the transform todetermine RR. In embodiments, the algorithm can also analyzerespiratory-induced motion components in the motion signal, and analyzethese along with components in the impedance waveform to determine RR.For example, the algorithm can deploy an adaptive filter, whereinoptical filter parameters are determined from a first waveform (e.g. themotion signal), and then applied to a second waveform (e.g. theimpedance waveform).

The invention has many advantages. In general, it combines a comfortablesensor system that resembles a conventional piece of jewelry, butincludes all the measurement electronics of a sophisticatedphysiological monitor. This system, referred to herein as the‘necklace’, is comfortable and easy to wear, thus improving patientcompliance. It integrates with a web-based software system that allows aclinician to monitor a robust set of physiological parameters from apatient, e.g. one suffering from CHF. The patient can be located athome, or in the hospital.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a three-dimensional image of the necklace according to theinvention that measures vital signs, hemodynamic parameters, andmotion/posture/activity level from an ambulatory patient;

FIG. 2 shows schematic drawings of the front and back of a patientwearing the necklace of FIG. 1;

FIG. 3 shows a schematic drawing of electrodes used for the ECG andimpedance systems positioned on the patient's chest using the sensor ofFIG. 1;

FIG. 4 shows how an optical sensor that connects to the necklace of FIG.1 measures SpO2 from a patient's earlobe;

FIG. 5 shows a time-dependent plot of a PPG waveform measured with theoptical sensor of FIG. 4;

FIGS. 6A and 6B show time-dependent plots of ECG and TBI waveformsfeaturing heartbeat-induced pulses (top) and a TBI waveform showingbreathing-induced oscillations, all measured with the necklace of FIG.1;

FIGS. 7A and 7B show correlation graphs of data, averaged from 39subjects, of baseline impedance (top) and SV (bottom) compared to lowerbody negative pressure (LBNP) level, which is an experimental techniquefor simulating CHF;

FIGS. 8A and 8B show graphs of Pearson's correlation coefficients (r),measured from each of the subjects used to generate the data for FIG. 7,describing the relationship of baseline impedance and SV to LBNP;

FIG. 9 shows a mechanical drawing of the sensor of FIG. 1 and itsassociated electrodes for ECG and impedance measurements;

FIG. 10 shows a mechanical drawing of the sensor of FIG. 1 and itsassociated electronics for ECG, impedance, and digital processingsystems;

FIG. 11 shows a mechanical drawing of the sensor of FIG. 1 and itsassociated battery and data-transfer systems;

FIG. 12 shows a schematic drawing of the sensor of FIG. 1 transmittingdata to a computer server using the patient's cellular telephone and/orpersonal computer;

FIG. 13 shows screen captures from a software application operating onthe cellular telephone of FIG. 12;

FIGS. 14A and 14B show a schematic drawing of an electrical circuit usedwithin the sensor of FIG. 1 to measure the impedance waveform; and

FIG. 15 shows a flow chart of an algorithm used to calculate SV andother physiological parameters during periods of motion.

DETAILED DESCRIPTION OF THE INVENTION

As described above, the necklace according to the invention provides asimple, easy-to-wear sensor that measures all vital signs (HR/PR, SpO2,RR, TEMP, and SBP/DBP), hemodynamic parameters (thoracic fluid levels,CO, SV), and motion-related parameters (posture, degree of motion,activity level, and falls). Perhaps the most complex measurement made bythe necklace is that for blood pressure, i.e. SBP and DBP. Theseparameters are determined from PTT separating heartbeat-induced pulsesin the ECG and TBI waveforms, coupled with a PP determined from SVdetermined from the TBI waveform. Using these measurement systems, thenecklace's measurement of SBP and DBP is both continuous and cuffless.

Also innovative is the necklace's measurement of SpO2. Here, an opticalsensor featuring red and infrared light-emitting diodes (LEDs) clips onto the patient's ear to measure PPG waveforms. These signals passthrough a flexible cable to circuitry within the necklace that processesthem to determine SpO2.

All analog and digital electronics associated with these measurementsare integrated into the strands of the necklace. This means a singlecomponent, shaped like a piece of conventional jewelry as opposed to abulky medical device, measures a robust set of parameters that cancharacterize a patient using both one-time and continuous measurements.Measurements can take place over just a few minutes or several hours,and are made in medical facilities and at home. The necklace includes asimple LED in its amulet to indicate high-level conditions (e.g.,red/yellow/green illuminations depending on the patient's health, asdetermined from the vital signs and hemodynamic parameters). Also in theamulet is a battery that is easily replaced for long-term, continuousmeasurements. The necklace includes a wireless transmitter (operatingBluetooth and/or 802.11a/b/g/n) that sends data to, e.g., a conventionalmobile device (e.g. cellular telephone, tablet computer, desktop/laptopcomputer, or plug-in hub).

More specifically, FIG. 1 shows the necklace 30 that, during use, iscomfortably worn around the patient's neck like a conventional necklace.In this design, the necklace's cable includes all circuit elements,which are typically distributed on an alternating combination of rigid,fiberglass circuit boards and flexible Kapton circuit boards. Typicallythese circuit boards are potted with a protective material, such assilicone rubber, to increase patient comfort and protect the underlyingelectronics. The battery for this design can be integrated directly intothe cable, or connect to the cable with a conventional connector, suchas a stereo-jack connector, micro-USB connector, or magnetic interface.

The necklace 30 is designed for patients suffering from CHF and othercardiac diseases, such as cardiac arrhythmias, as well as patients withimplanted devices such as pacemakers and ICDs. Using the magneticallyconnected electrodes described in more detail below, it makes impedancemeasurements to determine CO, SV, and fluid levels, and ECG measurementsto determine a time-dependent ECG waveform and HR. Additionally itmeasures RR, TEMP, SpO2, PR, location, and motion-related propertiessuch as posture, activity level, falls, and degree of motion. Thesensor's form factor is designed for both one-time measurements, whichtake just a few minutes, and continuous measurements, which can takeseveral days. Necklaces are likely familiar to a patient 10 wearing thissystem, and this in turn may improve their compliance in makingmeasurements as directed by their physician. Ultimately compliance inusing the necklace may improve the patient's physiological condition.Moreover, it is designed to make measurements near the center of thechest, which is relatively insensitive to motion compared to distalextremities, like the arms or hands. The necklace's form factor alsoensures relatively consistent electrode placement for the impedance andECG measurements; this is important for one-time measurements made on adaily basis, as it minimizes day-to-day errors associated with electrodeplacement. Finally, the necklace's form factor distributes electronicsaround the patient's neck, thereby minimizing bulk and clutterassociated with these components and making it more comfortable to thepatient.

In one embodiment the necklace 30 features a pair of electrode holders34A, 34B, located on opposing sides, that each include magnets asdescribed in more detail with respect to FIG. 9. The electrode holders34A, 34B each receive a separate 3-part magnetically connected electrodepatch 35, 37. During use, the electrode patches 35, 37 connect to theirrespective electrode holders 34A, 34B through the magnetic interface,and then stick to the patient's chest when the necklace 30 is drapedaround their neck. An adhesive backing supports each conductiveelectrode within the electrode patch 35, 37. The electrodes feature asticky, conductive gel that contacts the patient's skin. The conductivegel contacts a metal pad that is coated on one side with a thin layer ofAg/AgCl, and connects to a magnet through a via. As described in moredetail with respect to FIG. 3, the outer electrodes in each electrodepatch are used for the impedance measurement (they conduct signals V+/−,I+/−), while the inner electrodes are used for the ECG measurement (theyconduct signals ECG+/−). Proper spacing of the electrodes ensures bothimpedance and ECG waveforms having high signal-to-noise ratios; this inturn leads to measurements that are relatively easy to analyze, and thushave optimum accuracy. FIG. 9 shows preferred dimensions for thesecomponents.

A flexible, flat cable 38 featuring a collection of conductive memberstransmits signals from the electrode patches 35, 37 to an electronicsmodule 36, which, during use, is preferably worn near the back of theneck. Typically the cable 38 includes alternating regions of rigidfiberglass circuit boards 75A-D and flexible Kapton flex circuits 77A-Fto house other electronic components (used, e.g., for other measurementcircuits) and conduct electrical signals. The electronic module 36 maysnap into a soft covering to increase comfort. The electronics module 36features a first electrical circuit for making an impedance-basedmeasurement of TBI waveforms that yield CO, SV, RR, and fluid levels,and a second electrical circuit for making differential voltagemeasurements of ECG waveforms that yield HR and arrhythmia information.The first electrical circuit, which is relatively complex, is shownschematically in FIG. 14; the second electrical circuit is well known inthis particular art, and is thus not described in detail here.

FIG. 10 shows a more detailed view of the electronics module 36. Duringa measurement, the second electrical circuit 64 measures an analog ECGwaveform that is received by an internal analog-to-digital converterwithin a microprocessor 62. The microprocessor analyzes this signal tosimply determine that the electrode patches are properly adhered to thepatient, and that the system is operating satisfactorily. Once thisstate is achieved, the first 61 and second 64 electrical circuitsgenerate time-dependent analog waveforms that a high-resolutionanalog-to-digital converter 62 within the electronics module 36 receivesand then sequentially digitizes to generate time-dependent digitalwaveforms. Analog waveforms can be switched over to this component, forexample, using a field effect transistor (FET) 63. Typically thesewaveforms are digitized with 16-bit resolution over a range of about −5Vto 5V. The microprocessor 62 receives the digital waveforms andprocesses them with computational algorithms, written in embeddedcomputer code (such as C or Java), to generate values of CO, SV, fluidlevel, and HR. An example of an algorithm is described with reference toFIG. 15. Additionally, the electronics module 36 features a 3-axisaccelerometer 65 and temperature sensor 67 to measure, respectively,three time-dependent motion waveforms (along x, y, and z-axes) and TEMPvalues. The microprocessor 62 analyzes the time-dependent motionwaveforms to determine motion-related properties such as posture,activity level, falls, and degree of motion. Temperature values indicatethe patient's skin temperature, and can be used to estimate their coretemperature (a parameter familiar to physicians), as well as ancillaryconditions, such as perfusion, ambient temperature, and skin impedance.Motion-related parameters are determined using techniques known in theart. Temperature values are preferably reported in digital form that themicroprocessor receives through a standard serial interface, such asI2C, SPI, or UART.

Both numerical and waveform data processed with the microprocessor areported to a wireless transmitter 66, such as a transmitter based onprotocols like Bluetooth or 802.11a/b/g/n. From there, the transmittersends data to an external receiver, such as a conventional cellulartelephone, tablet, wireless hub (such as Qualcomm's 2Net system), orpersonal computer, as is shown in FIG. 12. Devices like these can serveas a ‘hub’ to forward data to an Internet-connected remote serverlocated, e.g., in a hospital, medical clinic, nursing facility, oreldercare facility.

Referring back to FIG. 1, and in more detail in FIG. 11, a batterymodule 32 featuring a rechargeable Li:ion battery 48 connects at twopoints to the cable 38 using a pair of connectors 79A, 79B. During use,the connectors 79A, 79B plug into a pair of mated connectors 44A, 44Bthat securely hold the terminal ends of the cable 38 so that thenecklace 30 can be comfortably and securely draped around the patient'sneck. Importantly, when both connectors 79A, 79B are plugged into thebattery module 32, the circuit within the necklace 30 is completed, andthe battery module 32 supplies power to the electronics module 36 todrive the above-mentioned measurements. The connectors 79A, 79Bterminating the cable can also be disconnected from the connectors 44A,44B on the battery module 32 so that this component can be replacedwithout removing the necklace 30 from the patient's neck. Replacing thebattery module 32 in this manner means the necklace 30 can be worn forextended periods of time without having to remove it from the patient.In general, the connectors 79A, 79B can take a variety of forms: theycan be flat, multi-pin connectors, such as those shown in FIG. 1, orstereo-jack type connectors, such as those shown in FIG. 11, thatquickly plug into a female adaptor. Both sets of connectors 79A, 79B,44A, 44B may also include a magnetic coupling so that they easily snaptogether, thereby making the sensor easy to apply. Typically an LED 27on the battery module indicates that this is the case, and that thesystem is operational. When the battery within battery module 32 isnearly drained, the LED 27 indicates this particular state (e.g., bychanging color, or blinking periodically). This prompts a user to unplugthe battery module 32 from the two connectors, plug it into a rechargecircuit (not shown in the figure), and replace it with a fresh batterymodule as described above. Also contained within the battery module is aflash memory card 23 for storing numerical and waveform data, and amicro-USB port 25 that connects to the flash memory card 23 fortransferring data to a remote computer 24. Typically the micro-USB port25 is also used for recharging the battery when the sensor is removedfrom the patient. In embodiments, these components can also be moved tothe electronics module 36.

As is clear from FIG. 1, the neck-worn cable 38 serves four distinctpurposes: 1) it transfers power from the battery module 32 to theelectronics module 36; 2) it ports signals from the electrode patches35, 37 to the impedance and ECG circuits; 3) it ensures consistentelectrode placement for the impedance and ECG measurements to reducemeasurement errors; and 4) it distributes the various electronicscomponents and thus allows the necklace to be comfortably worn aroundthe patient's neck. Typically each arm of the cable 38 will have sixwires: two for the impedance electrodes, one for the ECG electrode, andthree to pass signals from the electronics module to electricalcomponents within the battery module. These wires can be included asdiscrete elements, a flex circuit, or, as described above, a flexiblecable.

Non-flexible circuit board 75B includes a standard pulse oximetrycircuit, such as the one described in the following patent application,the contents of which are incorporated herein by reference: BODY-WORNPULSE OXIMETER, U.S.S.N. 20100324389, filed Sep. 14, 2009. The circuitdrives red and infrared LEDs in an alternating, pulsatile manner, andadditionally controls a light-sensitive diode. During a measurement, thelight-sensitive diode receives radiation from the LED that eithertransmits through or reflects off of tissue. Signals from thelight-sensitive diode pass through amplifier and filter circuitry toyield PPG waveforms emanating from the red and infrared radiation. Thesewaveforms are then digitized with an analog-to-digital converter, andthen processed to extract fiducial points as described in theabove-referenced patent application. The fiducial points are thenprocessed with an algorithm that operates Eq. 3, below, to determine aSpO2 value.

$\begin{matrix}{R = \frac{{{red}({AC})}/{{red}({DC})}}{{{infrared}({AC})}/{{infrared}({DC})}}} & (3)\end{matrix}$

In Eq. 3, the red(AC) and red (DC) represent, respectively, parametersextracted from the AC and DC components of the PPG waveform measuredwith the red LED. A similar case holds for the infrared(AC) andinfrared(DC) values. The term ‘AC’ signals, as used herein, refers to aportion of a PPG waveform that varies relatively rapidly with time, e.g.the portion of the signal originating by pulsations in the patient'sblood. ‘DC’ signals, in contrast, are portions of the PPG that arerelatively invariant with time, e.g. the portion of the signaloriginating from scattering off of components such as bone, skin, andnon-pulsating components of the patient's blood.

More specifically, AC signals are measured from a heartbeat-inducedpulse present in both waveforms. The pulse represents a pressure wave,launched by the heart, which propagates through the patient'svasculature and causes a time-dependent increase in volume in botharteries and capillaries. When the pressure pulse reaches vasculatureirradiated by the oximeter's optical system, a temporary volumetricincrease results in a relatively large optical absorption according tothe Beer-Lambert Law. DC signals originate from radiation scatteringfrom static components such as bone, skin, and relatively non-pulsatilecomponents of both arterial and venous blood. Typically only about0.5-1% of the total signal measured by the photodetector originates fromthe AC signal, with the remainder originating from the DC signal.Separation of AC and DC signals is typically done with both analog anddigital filtering techniques that are well-known in the art.

The R value in Eq. 3, which is sometimes called a ‘ratio of ratios’(RoR), represents a ratio of Hb to HbO2. It equates an actual SpO2value, which ranges from 0-100% O2, to an empirical relationship thatresembles a non-linear equation. Above about 70% O2 this equationtypically yields values that are accurate to a few percent. Measurementsbelow this value, while not necessarily accurate, still indicate ahypoxic patient in need of medical attention. Additional details forthis calculation are described in the above-referenced patentapplication.

As shown in FIG. 1, the pulse oximetry circuit within the circuit board75B connects through a cable 51 terminated with an optical sensor 50. Intypical embodiments, the optical sensor is in the form of a simple clipwherein the red 54 and infrared 55 LEDs are disposed on one arm of theclip, and the light-sensitive diode 56 is disposed on the opposing arm.The clip typically includes a spring-loaded mechanism so that it caneasily connect to the patient's ear 53, as shown in FIG. 4. Mostpreferably, the optical sensor 50 operates in a transmission mode,meaning the LEDs 54, 55 and light-sensitive diode 56 are positioned asdescribed above. Radiation from the diodes passes through tissue in theearlobe, and then arrives at the light-sensitive diode 56, where thiscomponent and the pulse oximetry circuit process it to form therequisite PPG waveforms needed for Eq. 3. Alternatively, the opticalsensor 50 can operate in a reflection mode, meaning the LEDs andlight-sensitive diode are disposed on the same side of the sensor 50,and radiation emitted from the LEDs reflects off a surface of theearlobe before arriving at the light-sensitive diode. In this case, theradiation interacts with a thin layer of tissue, where it is modulatedaccordingly to form the PPG waveforms.

FIG. 5 shows a conventional PPG waveform measured with theabove-described optical sensor. It features a sequence ofheartbeat-induced pulses, with the time duration separating the pulsesbeing inversely related to PR. The heartbeat-induced pulses representblood pulsing in an underlying artery that absorbs (or reflects)incident radiation from the red and infrared LEDs. The PPG waveform alsoincludes a slowly varying baseline that is due to underlying opticalabsorption by the blood. PPG waveform emanating from both waveforms looksimilar, with that from infrared radiation typically having a relativelyhigh signal-to-noise ratio.

FIG. 2 shows the above-described necklace 30 worn around the neck of apatient 10. As described above, it includes an electronics module 36worn on the back of the patient's neck, a battery module 32 in thefront, and electrode holders 34A, 34B that connect to the magneticallyactive electrode patches 35, 37 and secure the cable 38 around thepatient's neck that make impedance and ECG measurements.

As shown in the figure, the necklace 30 drapes around the patient's neckso that non-flexible circuit boards 75B, 75C are disposed on opposingsides. Within the circuit board 75B is the above-described pulseoximetry circuit. The cable 51 plugs into a connector on the circuitboard 75B so that it can be easily detached. With this configuration,the optical sensor 50 can comfortably connect to the patient's earlobeto measure SpO2 values in an effective manner that minimizes cableclutter, and frees the patient's hands and fingers (where pulse oximetryvalues are normally made) for other purposes. An added benefit of theconfiguration shown in FIG. 2 is the reduction of motion artifacts,which can distort PPG waveforms, thus resulting in erroneous SpO2values. During everyday activities, the head and neck typically moveless than the hands and fingers. This means that a sensor configurationlike that shown in FIG. 2 is less susceptible to motion-relatedartifacts than one where the optical sensor is worn on the patient'sfinger. Ultimately this improves the accuracy of SpO2 values measuredfrom the patient.

FIG. 3 indicates in more detail how the above-described electrodemeasures TBI waveforms and CO/SV values from a patient. As describedabove, 3-part electrode patches 35, 37 within the neck-worn sensorattach to the patient's chest. Ideally, each patch 35, 37 attaches justbelow the collarbone near the patient's left and right arms. During ameasurement, the impedance circuit injects a high-frequency,low-amperage current (I) through outer electrodes 31C, 41C, 41A, 31A.Typically the modulation frequency is about 70 kHz, and the current isabout 4 mA. The current injected by electrodes 31A, 31C is out of phaseby 180 degrees from that injected by electrodes 41A, 41C. It encountersstatic (i.e. time-independent) resistance from components such as bone,skin, and other tissue in the patient's chest. Additionally, blood andfluids in the chest conduct the current to some extent. Blood ejectedfrom the left ventricle of the heart into the aorta, along with fluidsaccumulating in the chest, both provide a dynamic (i.e. time-dependent)resistance. The aorta is the largest artery passing blood out of theheart, and thus it has a dominant impact on the dynamic resistance;other vessels, such as the superior vena cava, will contribute in aminimal way to the dynamic resistance.

Inner electrodes 31B, 41B measure a time-dependent voltage (V) thatvaries with resistance (R) encountered by the injected current (I). Thisrelationship is based on Ohm's Law, shown below in Eq. 4:

V=I×R   (4)

During a measurement, the time-dependent voltage is filtered by theimpedance circuit, and ultimately measured with an analog-to-digitalconverter within the electronics module. This voltage is then processedto calculate SV with an equation such as that shown below in Eq. 5,which is the Sramek-Bernstein equation, or a mathematical variationthereof. Historically, parameters extracted from TBI signals are fedinto the equation, shown below, which is based on a volumetric expansionmodel taken from the aortic artery:

$\begin{matrix}{{SV} = {\delta\frac{L^{3}}{{4.2}5}\frac{\left( {d{{Z(t)}/d}t} \right)_{\max}}{Z_{0}}{LVET}}} & (5)\end{matrix}$

In Eq. 5, Z(t) represents the TBI waveform, δ represents compensationfor body mass index, Zo is the base impedance, L is estimated from thedistance separating the current-injecting and voltage-measuringelectrodes on the thoracic cavity, and LVET is the left ventricularejection time, which is the time separating the opening and closing ofthe aortic valve, and can be determined from the TBI waveform, or fromthe HR using an equation called ‘Weissler's Regression’, shown below inEq. 6, that estimates LVET from HR:

LVET=−0.0017×HR+0.413   (6)

Weissler's Regression allows LVET, to be estimated from HR determinedfrom the ECG waveform. This equation and several mathematicalderivatives, along with the parameters shown in Eq. 5, are described indetail in the following reference, the contents of which areincorporated herein by reference: ‘Impedance Cardiography, Pulsatileblood flow and the biophysical and electrodynamic basis for the strokevolume equations’, Bernstein, Journal of Electrical Bioimpedance, Vol.1, p. 2-17, 2010. Both the Sramek-Bernstein Equation and an earlierderivative of this, called the Kubicek Equation, feature a ‘staticcomponent’, Z₀, and a ‘dynamic component’, ΔZ(t), which relates to LVETand a (dZ/dt)_(max)/Z_(o) value, calculated from the derivative of theraw TBI signal, □Z(t). These equations assume that(dZ(t)/dt)_(max)/Z_(o) represents a radial velocity (with units of Ω/s)of blood due to volume expansion of the aorta.

In Eq. 5 above, the parameter Z₀ will vary with fluid levels. Typicallya high resistance (e.g. one above about 30Ω) indicates a dry, dehydratedstate. Here, the lack of conducting thoracic fluids increasesresistivity in the patient's chest. Conversely, a low resistance (e.g.one below about 19Ω) indicates the patient has more thoracic fluids, andis possibly overhydrated. In this case the abundance of conductingthoracic fluids decreases resistivity in the patient's chest. The TBIcircuit and specific electrodes used for a measurement may affect thesevalues. Thus, the values can be more refined by conducting a clinicalstudy with a large number of subjects, preferably those in variousstates of CHF, and then empirically determining ‘high’ and ‘low’resistance values.

FIG. 6 shows derivatized TBI and ECG waveforms measured with thenecklace of FIG. 1 plotted over a short (about 5 seconds) time window(top), and TBI waveforms plotted over a longer window (bottom, 60seconds). Referring first to the top portion of the figure, individualheartbeats produce time-dependent pulses in both the ECG and TBIwaveforms. The TBI waveform shown in the figure is the firstmathematical derivative of a raw TBI waveform. As is clear from thedata, pulses in the ECG waveform precede those in the TBI waveform. TheECG pulses, each featuring a sharp, rapidly rising QRS complex, indicateinitial electrical activity in contractions in the patient's heart, and,informally, the beginning of the cardiac cycle. The QRS complex is thepeak of the ECG waveform. TBI pulses follow the QRS complex by about 100ms, and indicate blood flow through arteries in the patient's thoraciccavity. These signals are dominated by contributions from the aorta,which is the largest artery in this region of the body. During aheartbeat, blood flows from the patient's left ventricle into the aorta.The volume of blood is the SV. Blood flow enlarges this vessel, which istypically very flexible, and also temporarily aligns blood cells (callederythrocytes) from their normally random orientation. Both of thesemechanisms—enlargement of the aorta and temporary alignment of theerythrocytes—improve electrical conduction near the aorta, thusdecreasing the electrical impedance as measured with TBI. The waveformshown in the upper portion of FIG. 6 is a first derivative of the rawTBI waveform, meaning its peak represents the point of maximum impedancechange.

A variety of time-dependent parameters can be extracted from the ECG andTBI waveforms. For example, as shown in the upper portion of the figure,it is well known that HR can be determined from the time separatingneighboring ECG QRS complexes. Likewise, LVET can be measured directlyfrom the TBI pulse. LVET is measured from the onset of the derivatizedpulse to the first positive going zero crossing. Also measured from thederivatized TBI pulse is (dZ/dt)_(max), a parameter that is used tocalculate SV, as shown in Eq. 5 and described in more detail in thereference described above.

The time difference between the ECG QRS complex and the peak of thederivatized TBI waveform represents a PTT. This value can be calculatedfrom other fiducial points, particularly on the TBI waveform (such asthe base or midway point of the heartbeat-induced pulse). But typicallythe peak of the derivatized waveform is used, as it is relatively easyto develop a software beat-picking algorithm that finds this fiducialpoint.

PTT correlates inversely to SBP and DBP, as shown below in Eqs. 7-8,where m_(SBP) and DBP are patient-specific slopes for, respectively, SBPand DBP, and SBP_(cal) and DBP_(cal) are values, respectively, of SBPand DBP measured during a calibration measurement. Without thecalibration PTT only indicates relative changes in SBP and DBP. Acalibration can be provided with conventional means, such as anoscillometric blood pressure cuff or in-dwelling arterial line. Thecalibration yields both the patient's immediate value of SBP and DBP.Multiple values of PTT and blood pressure can be collected and analyzedto determine patient-specific slopes m_(SBP) and m_(DBP), which relatechanges in PTT with changes in SBP and DBP. The patient-specific slopescan also be determined using pre-determined values from a clinicalstudy, and then combining these measurements with biometric parameters(e.g. age, gender, height, weight) collected during the clinical study.

$\begin{matrix}{{SBP} = {\frac{m_{SBP}}{PTT} + {SBP_{cal}}}} & (7) \\{{DBP} = {\frac{m_{DBP}}{PTT} + {DBP_{cal}}}} & (8)\end{matrix}$

In embodiments, waveforms like those shown in the upper portion of FIG.6 are processed to determine PTT, which is then used to determine eitherSBP or DBP according to Eqs. 7 or 8. Typically PTT and SBP correlatebetter than PTT and DBP, and thus this parameter is first determined.Then PP is estimated from SV, calculation of which is described below.Most preferably, instant values of PP and SV are determined,respectively, from the blood pressure calibration and from the TBIwaveform.

PP can be estimated from either the absolute value of SV, SV modified byanother property (e.g. LVET), or the change in SV. In the first method,a simple linear model is used to process SV (or, alternatively, SV×LVET)and convert it into PP. The model uses the instant values of PP and SV,determined as described above from a calibration measurement, along witha slope that relates PP and SV (or SV×LVET). The slope can be estimatedfrom a universal model that, in turn, is determined using a populationstudy. Alternatively, a slope tailored to the individual patient isused. Such a slope can be selected, for example, using biometricparameters describing the patient, as described above. Here, PP/SVslopes corresponding to such biometric parameters are determined from alarge population study, and then stored in computer memory on thenecklace. When a necklace is assigned to a patient, their biometric datais entered into the system, e.g. using a mobile telephone that transmitsthe data to a microprocessor in the necklace via Bluetooth. Then analgorithm on the necklace processes the data and selects apatient-specific slope. Calculation of PP from SV is described in thefollowing reference, the contents of which are incorporated herein byreference: ‘Pressure-Flow Studies in Man. An Evaluation of the Durationof the Phases of Systole’, Harley et al., Journal of ClinicalInvestigation, Vol. 48, p. 895-905, 1969. As described in thisreference, the relationship between PP and SV for a given patienttypically has a correlation coefficient (r) that is greater than 0.9,which indicates excellent agreement between these two properties.Similarly, in the above-mentioned reference, SV is shown to correlatewith the product of PP and LVET, with most patients showing an r valueof greater than 0.93, and the pooled correlation value (i.e. that forall subjects) being 0.77. This last result indicates that a singlelinear relationship between PP, SV, and LVET may hold for all patients.

More preferably, PP is determined from SV using relative changes inthese values. Typically the relationship between the change in SV andchange in PP is relatively constant across all subjects. Thus, similarto the case for PP, SV, and LVET, a single, linear relationship can beused to relate changes in SV and changes in PP. Such a relationship isdescribed in the following reference, the contents of which areincorporated herein by reference: ‘Pulse pressure variation and strokevolume variation during increased intra-abdominal pressure: anexperimental study’, Didier et al., Critical Care, Vol. 15:R33, p. 1-9,2011. Here, the relationship between PP variation and SV variation for67 subjects displayed a linear correlation of r=0.93, and extremely highvalue for pooled results that indicates a single, linear relationshipmay hold for all patients.

From such a relationship, PP is determined from the TBI-based SVmeasurement, and SBP is determined from PTT. DBP is then calculated fromSBP and PP.

The necklace determines RR from both the TBI waveform, and from a motionwaveform generated by the accelerometer (called the ACC waveform), whichis typically located in analog circuitry within the necklace, asdescribed above. The bottom portion of FIG. 6 indicates how the TBIwaveform yields RR. In this case, the patient's respiratory effort movesair in and out of the lungs, thus changing the impedance in the thoraciccavity. This time-dependent change maps onto the TBI waveform, typicallyin the form of oscillations or pulses that occur at a much lowerfrequency than the heartbeat-induced cardiac pulses shown in the upperpart of FIG. 5. Simple signal processing (e.g. filtering, beat-picking)of the low-frequency, breathing-induced pulses in the waveform yieldsRR.

Likewise, the ACC waveform will reflect breathing-induced movements inthe patient's chest. This results in pulses within the waveform thathave a similar morphology to those shown in the lower portion of FIG. 6for the TBI waveform. Such pulses can be processed as described above toestimate RR. RR determined from the ACC waveform can be used by itself,or processed collectively with RR determined from the TBI waveform(e.g., using adaptive filtering) to improve accuracy. Such an approachis described in the following patent application, the contents of whichare incorporated herein by reference: BODY-WORN MONITOR FOR MEASURINGRESPIRATION RATE, U.S.S.N. 20110066062, Filed Sep. 14, 2009.

As shown in the lower portion of FIG. 6, the baseline of the TBIwaveform, called Zo, can be easily determined. Zo is used to determineSV, as described above in Eq. 5.

FIGS. 7 and 8 show how a process called lower body negative pressure(LBNP) affects baseline impedance Zo and SV. LBNP serves as a surrogatefor hemorrhage, a process that typically results in dramatic changes inSV. FIG. 7 shows pooled results from 39 subjects undergoing a gradualincrease in LBNP from 0 mmHg (i.e. no change from ambient) to a vacuumof 60 mmHg (corresponding to a loss of blood of about 2 L). The datashown in this figure are averaged over all 39 subjects, and impedancewaveforms similar to those described above were measured from thethoracic cavity and analyzed to determine SV and thoracic fluid level.As shown in the top portion of the figure, the change in baselineimpedance correlates in a linear manner with the LBNP level, with theagreement between these parameters (Pearson's correlation coefficientr²=0.9998) being extremely high. Here, vacuum applied during LBNPgradually removes conductive fluids from the thoracic cavity, thusdecreasing conductivity and increasing baseline impedance. Similarly,the relationship between LBNP level and SV shown in the bottom half ofthe plot is also linear, with the slope going in the opposite directionas that for the impedance/LBNP correlation. In this case increasing LBNPremoves blood from the patient's thoracic cavity, thus reducing theireffective blood volume (called ‘pre-load’) and essentially simulatinghemorrhage. During hemorrhage, the body is trained to reduce blood flowby decreasing the amount of blood pumped by the heart (the SV) topreserve perfusion of the internal organs. Thus, it is expected thatincreasing LBNP will systematically decrease SV, which is exactly whatis shown in the lower half of FIG. 7. The correlation for thisrelationship is also quite high, with r²=0.99531.

In conclusion, the results shown in FIG. 7 indicate that two parametersthat change with the onset of CHF—thoracic fluid level and SV—can beaccurately measured with an impedance-based technique, such as thatdeployed with the sensor described herein.

The data shown in FIG. 7 are averaged over all 39 subjects, while theindividual correlation coefficient for each subject for theabove-described measurements are shown in FIG. 8. As is clear from thesedata, 36 out of 39 subjects show a correlation between LBNP level(representing a proxy for fluid level, as described above) and baselineimpedance characterized by r>0.98, which is extremely high. Similarly,36 out of 39 subjects show a correlation between LBNP level and SVcharacterized by r>0.9. Both of these plots indicate that the parametersmeasured by impedance measurements show promise for being an accuratephysiological monitor.

FIG. 12 depicts how the necklace 30 shown in FIG. 1 is designed tofacilitate remote monitoring of a patient 10. As shown in the topportion of the figure, after the necklace 30 measures the patient, itautomatically transmits data through its internal Bluetooth wirelesstransmitter to the patient's cellular telephone 20. In this case, thecellular telephone 20 preferably runs a downloadable softwareapplication that accesses the phone's internal Bluetooth drivers, andincludes a simple patient-oriented application that renders data on thephone's screen. From there, using its internal modem, the cellulartelephone 20 transmits data to an IP address associated with a computerserver 22. The computer server 22, in turn, renders a web-based systemthat displays data for clinicians at a hospital, medical clinic, nursingfacility, or eldercare facility. The web-based system may show ECG andTBI waveforms, trended numerical data, the patient's medical history,along with their demographic information. A clinician viewing theweb-based system may, for example, analyze the data and then call thepatient 10 and have them adjust their medications or diet.Alternatively, as shown in the lower half of the figure, the necklace 30can automatically transmit data through Bluetooth to a personal computer24, which then uses a wired or wireless Internet connection to transmitdata to the computer server 22. Here, the personal computer 24 runs acustom software program to download data from the sensor 22, display itfor the patient in an easy-to-understand format, and then forward it tothe computer server for a relatively complex analysis as describedabove. In yet another embodiment, the necklace 30 is directly pluggedinto the personal computer 24 through a USB connection, and data aredownloaded using a wired connection and forwarded to the computer server22 as described above.

FIG. 13 shows examples of user interfaces 90, 91, 92 that integrate withthe above-mentioned systems and run on the cellular telephone 20, shownin this case as an iPhone. The user interfaces show information such aspatient demographics (interface 90), patient-oriented messages(interface 91), and numerical vital signs and time-dependent waveforms(interface 92). The interfaces shown in the figures are designed for thepatient. More screens, of course, can be added, and similar interfaces(preferably with more technical detail) can be designed for the actualclinician. The interfaces can also be used to render operationalreports, which are then sent off to a clinician for review.

FIG. 14 shows an analog circuit 100 that performs the impedancemeasurement according to the invention. The figure shows just oneembodiment of the circuit 100; similar electrical results can beachieved using a design and collection of electrical components thatdiffer from those shown in the figure.

The circuit 100 features a first magnetically connected electrode 115Athat injects a high-frequency, low-amperage current (I₁) into thepatient's brachium. This serves as the current source. Typically acurrent pump 102 provides the modulated current, with the modulationfrequency typically being between 50-100 KHz, and the current magnitudebeing between 0.1 and 10 mA. Preferably the current pump 102 suppliescurrent with a magnitude of 4 mA that is modulated at 70 kHz through thefirst electrode 115A. A second magnetically connected electrode 117Ainjects an identical current (I₂) that is out of phase from I₁ by 180°.

Another pair of magnetically connected electrodes 115B, 117B measure thetime-dependent voltage encountered by the propagating current. Theseelectrodes are indicated in the figure as V+ and V−. As described above,using Ohm's law, the measured voltage divided by the magnitude of theinjected current yields a time-dependent resistance to ac (i.e.impedance) that relates to blood flow in the aortic artery. As shown bythe waveform 128 in the figure, the time-dependent resistance features aslowly varying dc offset, characterized by Zo, that indicates thebaseline impedance encountered by the injected current; for TBI thiswill depend, for example, on the amount of thoracic fluids, along withthe fat, bone, muscle, and blood volume in the chest of a given patient.Zo, which typically has a value between about 10 and 150Ω, is alsoinfluenced by low-frequency, time-dependent processes such asrespiration. Such processes affect the inherent capacitance near thechest region that TBI measures, and are manifested in the waveform bylow-frequency undulations, such as those shown in the waveform 128. Arelatively small (typically 0.1-0.5Ω) AC component, ΔZ(t), lies on topof Zo and is attributed to changes in resistance caused by theheartbeat-induced blood that propagates in the brachial artery, asdescribed in detail above. □Z(t) is processed with a high-pass filter toform a TBI signal that features a collection of individual pulses 130that are ultimately processed to determine SV and CO.

Voltage signals measured by the first electrode 115B (V+) and the secondelectrode 117B (V−) feed into a differential amplifier 107 to form asingle, differential voltage signal which is modulated according to themodulation frequency (e.g. 70 kHz) of the current pump 102. From there,the signal flows to a demodulator 106, which also receives a carrierfrequency from the current pump 102 to selectively extract signalcomponents that only correspond to the TBI measurement. The collectivefunction of the differential amplifier 107 and demodulator 106 can beaccomplished with many different circuits aimed at extracting weaksignals, like the TBI signal, from noise. For example, these componentscan be combined to form a ‘lock-in amplifier’ that selectively amplifiessignal components occurring at a well-defined carrier frequency. Or thesignal and carrier frequencies can be deconvoluted in much the same wayas that used in conventional AM radio using a circuit that features oneor more diodes. The phase of the demodulated signal may also be adjustedwith a phase-adjusting component 108 during the amplification process.In one embodiment, the ADS1298 family of chipsets marketed by TexasInstruments may be used for this application. This chipset featuresfully integrated analog front ends for both ECG and impedancepneumography. The latter measurement is performed with components fordigital differential amplification, demodulation, and phase adjustment,such as those used for the TBI measurement, that are integrated directlyinto the chipset.

Once the TBI signal is extracted, it flows to a series of analog filters110, 112, 114 within the circuit 100 that remove extraneous noise fromthe Zo and ΔZ(t) signals. The first low-pass filter 110 (30 Hz) removesany high-frequency noise components (e.g. power line components at 60Hz) that may corrupt the signal. Part of this signal that passes throughthis filter 110, which represents Zo, is ported directly to a channel inan analog-to-digital converter 120. The remaining part of the signalfeeds into a high-pass filter 112 (0.1 Hz) that passes high-frequencysignal components responsible for the shape of individual TBI pulses130. This signal then passes through a final low-pass filter 114 (10 Hz)to further remove any high-frequency noise. Finally, the filtered signalpasses through a programmable gain amplifier (PGA) 116, which, using a1.65V reference, amplifies the resultant signal with acomputer-controlled gain. The amplified signal represents ΔZ(t), and isported to a separate channel of the analog-to-digital converter 120,where it is digitized alongside of Zo. The analog-to-digital converterand PGA are integrated directly into the ADS1298 chipset describedabove. The chipset can simultaneously digitize waveforms such as Zo andΔZ(t) with 24-bit resolution and sampling rates (e.g. 500 Hz) that aresuitable for physiological waveforms. Thus, in theory, this one chipsetcan perform the function of the differential amplifier 107, demodulator108, PGA 116, and analog-to-digital converter 120. Reliance of just asingle chipset to perform these multiple functions ultimately reducesboth size and power consumption of the TBI circuit 100.

Digitized Zo and Z(t) waveforms are received by a microprocessor 124through a conventional digital interface, such as a SPI or I2Cinterface. Algorithms for converting the waveforms into actualmeasurements of SV and CO are performed by the microprocessor 124. Themicroprocessor 124 also receives digital motion-related waveforms froman on-board accelerometer 122, and processes these to determineparameters such as the degree/magnitude of motion, frequency of motion,posture, and activity level.

FIG. 15 shows a flow chart of an algorithm 133A that functions usingcompiled computer code that operates, e.g., on the microprocessor 124shown in FIG. 6. The algorithm 133A is used to measure TBI waveforms inthe presence of motion. The compiled computer code is loaded in memoryassociated with the microprocessor, and is run each time a TBImeasurement is converted into a numerical value for CO and SV. Themicroprocessor typically runs an embedded real-time operating system.The compiled computer code is typically written in a language such as C,C++, Java, or assembly language. Each step 135-150 in the algorithm 133Ais typically carried out by a function or calculation included in thecompiled computer code.

Algorithms similar to that shown in FIG. 15 can be used to calculateother physiological parameters in the presence of motion, such as SpO2,RR, HR, and PR.

In other embodiments, algorithms can process other waveforms, such asthe PPG and ECG waveforms, to extract parameters such as RR. Here, thelow-frequency envelope of the waveform indicates RR. In otherembodiments, a reflective pulse oximetry system can measure SpO2 withoutrequiring an ear-worn optical sensor, such as that shown in FIG. 4. Inthis case the sensor uses reflective-mode optical configurations tomeasure both the red and infrared PPG waveforms. In still otherembodiments, the electronics within the necklace, as shown in FIGS. 10and 11, are moved within the necklace's geometry. For example, they canbe moved from the back portion of the necklace to a side portionproximal to the front of the patient's neck.

Still other embodiments are within the scope of the following claims.

What is claimed is:
 1. A system adapted to be worn entirely on apatient's body for measuring both an impedance-related parameter and asecond physiological parameter, comprising: an optical system adapted tobe worn on a location of the body other than the patient's hands orfingers and comprising an optical circuit connected to an optical sensorcomprising a light source and an optical detector, the optical circuitconfigured to generate a waveform representing a signal generated withthe light source; an impedance system adapted to be worn on thepatient's body without wrapping around the body and connected to a firstelectrode that injects electrical current into the patient, and a secondelectrode that senses an impedance signal from the patient that resultsfrom the injected current; a digital processing system adapted to beworn on the patient's body without wrapping around the body, and adaptedto attach to the body by the first and second electrodes, the digitalprocessing system comprising a microprocessor configured to receive thewaveform, or a processed version thereof, and configured to process thewaveform, or a processed version thereof, to generate the secondphysiological parameter, and further configured to receive the impedancesignal and process it, or processed versions thereof, to generate theimpedance-related parameter, and, a flexible component adapted to attachto the patient's body using the first and second electrodes andcontaining a first distal end and a second distal end, the flexiblecomponent connected to the optical circuit, the impedance system, andthe digital processing system.
 2. The system of claim 1, wherein thesecond physiological parameter is pulse rate.
 3. The system of claim 1,wherein the light source is configured to operate in the red spectralregion.
 4. The system of claim 3, further comprising a second lightsource configured to operate in the infrared spectral region.
 5. Thesystem of claim 4, wherein the second light source configured to operatein the infrared spectral waveform generates a second waveform.
 6. Thesystem of claim 5, wherein the microprocessor is further configured toreceive the waveform and the second waveform, or processed versionsthereof, and is further configured to process the waveform and thesecond waveform, or processed versions thereof, to generate the secondphysiological parameter.
 7. The system of claim 6, wherein the secondphysiological parameter is pulse oximetry.
 8. The system of claim 1,wherein the flexible component couples the optical circuit to thedigital processing system.
 9. The system of claim 1, wherein theflexible component comprises a flexible circuit that connects theoptical circuit to the digital processing system.
 10. The system ofclaim 1, wherein the flexible component comprises at least twonon-flexible circuit boards connected to each other with a flexibleconductor.
 11. The system of claim 10, wherein the optical circuit iscomprised by a first non-flexible circuit board, and the digitalprocessing system is comprised by a second non-flexible circuit board.12. The system of claim 10, wherein the flexible conductor is a flexiblecircuit.
 13. The system of claim 10, wherein the flexible conductor is aplurality of wires.
 14. The system of claim 1, wherein the opticalcircuit comprises a first connector, and the flexible componentcomprises a second connector mated to the first connector.
 15. Thesystem of claim 1, wherein the optical sensor comprises a clipconfigured to attach to the patient's ear.
 16. The system of claim 1,wherein the optical sensor comprises an adhesive component configured toattach to the patient's ear.
 17. The system of claim 1, wherein theflexible component comprises a battery system.
 18. The system of claim17, wherein the flexible component comprises a first connector and thebattery system comprises a second connector, with the first connectormated to the second connector so that the battery system can bedetachably removed.
 19. The system of claim 1, further comprising awireless transceiver that is one of a Bluetooth transceiver and an802.11-based transceiver.
 20. The system of claim 1, further comprisingan ECG system, housed in the flexible component.